Table 4. Summary associations between maternal smoking and CHDs.
| Level I evidence (OCEBM) | Relative effect: Summary OR (95% CI) (unless otherwise specified) | No. of studies (offspring if reported) | Model: FE or RE, adjustment | Heterogeneity: χ2 I2 (%) |
| Any smoking during pregnancy (referent no smoking) | ||||
| Hackshaw (2011), smoking any time during pregnancy | ||||
| All | 1.09 (1.02 to 1.17) | 25 (2, 116, 757) | RE, 11 no adjustment, variables adjusted or matched varied across remaining studies included* | I2 64 |
| Lee (2013) (RR), smoking any time during pregnancy | ||||
| All | 1.11 (1.02 to 1.21) | 19 (18, 282 cases) | RE, 7 no adjustment, 12 adjusted for various variables, included† or matched cases and controls on some characteristics‡ | I2 NR |
| Nicoletti (2014), smoking any time during pregnancy | ||||
| All | 1.11 (1.03 to 1.19) | 29 (32, 000 cases) | RE, adjustment variables NR | I2 58 |
| Zhang (2017)§ (RR), smoking any time during pregnancy | ||||
| All | 1.11 (1.04 to 1.18) | 23 | RE, 14 no adjustment, 9 adjusted, variables varied across remaining included¶ | I2 69 |
| Europe | 1.12 (0.99 to 1.26) | 10 | RE | I2 74 |
| USA | 1.10 (1.03 to 1.18) | 11 | RE | I2 59 |
| Asia | 6.60 (2.13 to 20.59) | 2 | RE | I2 0 |
| Case control | 1.11 (1.03 to 1.20) | 19 | RE | I2 67 |
| Cohort studies | 1.13 (0.98 to 1.29) | 4 | RE | I2 79 |
| Age adjusted | 1.11 (1.02 to 1.20) | 10 | RE | I2 74 |
| BMI adjusted | 1.04 (0.97 to 1.11) | 3 | RE | I2 45 |
| Alcohol adjusted | 1.04 (0.98 to 1.10) | 4 | RE | I2 24 |
| Vitamin B-adjusted | 1.05 (0.97 to 1.12) | 5 | RE | I2 40 |
| Social factor adjusted | 1.05 (0.98 to 1.13) | 4 | RE | I2 12 |
| Wu (2023), smoking any time during pregnancy | ||||
| All | 1.16 (1.07 to 1.25) | 32 studies (33 cohorts) | RE, 17 no adjustment, variables varied across remaining, included** | I2 71 |
| Adjusted | 1.16 (1.06 to 1.27) | NR | RE | I2 73 |
| Not adjusted | 1.15 (0.99 to 1.34) | NR | RE | I2 70 |
| Cohort | 1.08 (0.98 to 1.20) | NR | RE | I2 50 |
| Case control | 1.17 (1.06 to 1.29) | NR | RE | I2 73 |
Maternal age, parity or gravidity, social class, race/ethnicity, maternal alcohol use, birth month or year, location or study centre, marital status, maternal or paternal education, previous induced abortions, mother’s occupation, caffeine, infant gender, kidney a/dysegenesis of infant, maternal diabetes, BMI, periconceptional multivitamin supplementation including folic acid, dietary folate intake, family history of malformations, and location (rural/urban setting).
Maternal age, maternal race/ethnicity, marital status, maternal education, parity, alcohol consumption, coffee consumption, infant’s year/month of birth, maternal diabetes (pregestational or gestational), interval between end of pregnancy and blood collection, homocysteine levels, folic acid intake/dietary folate, infant gender, maternal body mass indexBMI, family history of congenital defectCHDs, maternal occupation, infant race/ethnicity, therapeutic drug use, influenza-like illness, paternal smoking, cases and controls matched on birth hospital/geographic region, birth month/age, influenza-like illness, paternal smoking.
Cases and controls matched on birth hospital/geographical region, birth month/age race, or sex (2 studies).
This review excluded the following CHD types in the overall meta-analysis: ASD, AVSD, CHD, CTD, LVOTO, RVOTO, SPD, TGA, TOF, VSD: ASD, atrial septal defect;.AVSD, atrioventricular septal defect; CHD, congenital defect; CTD, conotruncal defect;LVOTO, left ventricular outflow tract obstruction; RVOTO, right ventricular outflow tract obstruction; SPD, septal defect; TGA, transposition of the great arteries; TOF, tetralogy of Fallot; VSD, ventricular septal defect.
Included maternal age, education level, folic acid use, periconceptional alcohol consumption, time interval between end of pregnancy and blood collection, serum homocysteine, folate, H vitamin B12 level, race, Hhomocysteine, methionine, occupation, M MTHFR:677 C>T, vitamin B 12, CysGly or cysteine, BMI, birth year, maternal education, therapeutic drug exposure during pregnancy, pre-gestational diabetes, influenza-like illness in the first trimester, parity, paternal smoking, offspring gender, prematurity, diabetes, adenosine, GluCys, study centre, birth defect history in first-degree relative, gravidity.
Included education, ethnicity, maternal age, coffee, maternal vitamin use, alcohol use, gravidity, year of birth, parity, gestational age, birth weight, diabetes, maternal BMI, infant gender, folic acid intake, hypertension, any binge drinking and smoking interaction term, low socio-economic status, stress, family income, socio-economic deprivation of the area of residence, pesticide exposure, organic solvents, family history of congenital anomalies, paternal age, and paternal smoking.
ASDatrial septal defectAVSDatrioventricular septal defectBMIbody mass indexCHDcongenital heart defectCTDconotruncal heart defectFEfixed effectsLVOTOleft ventricular outflow tract obstructionRErandom effectsRRrisk ratioRVOTO right ventricular outflow tract obstructionSPDseptal defectTGAtransposition of the great arteriesTOFtetralogy of FallotVSD ventricular septal defect